Cerebrospinal Fluid Cortisol and Progesterone Profiles and Outcomes Prognostication after Severe Traumatic Brain Injury
Cerebrospinal Fluid Cortisol and Progesterone Profiles and Outcomes Prognostication after Severe Traumatic Brain Injury
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DOI：
10.1089/neu.2013.3177
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发表时间：
2014-04-15
影响因子：
4.2
通讯作者：
Wagner, Amy K.
中科院分区：
文献类型：
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作者：
Santarsieri, Martina;Niyonkuru, Christian;Wagner, Amy K.
尽管在头部创伤的管理方面取得了重大进展，但仍然缺乏创伤性脑损伤（TBI）的药物治疗选择。虽然黄体酮的临床试验显示出希望，但皮质类固醇的试验失败了。本研究的目的是（1）表征TBI后内源性脑脊液（CSF）孕酮和皮质醇水平，（2）确定CSF和血清谱之间的关系，（3）评估这些激素作为长期预后预测因子的效用。我们评估了130名患有严重TBI的成年人。伤后6天收集血清样本（n=538）和CSF样本（n=746），分析皮质醇和孕酮，并与健康对照组（n=13）进行比较。激素数据与临床数据相关，包括6个月和12个月时的格拉斯哥结局量表（GOS）评分。组为基础的轨迹（TRAJ）分析用于开发时间激素轮廓描绘不同的亚群。与对照组相比，脑外伤后第一周脑脊液皮质醇水平显著且持续升高，高水平的脑脊液皮质醇水平与不良预后相关。作为皮质醇的前体，孕酮介导了这些作用。脑外伤后血清和脑脊液中皮质醇和孕酮的水平与对照组有很强的相关性，这可能是因为血脑屏障的破坏。此外，TBI后差异受损的激素转运和代谢机制，脑内类固醇的潜在从头合成，以及皮质醇和促炎细胞因子的复杂相互作用可以解释这些急性激素谱，并且当结合在一起时，可能有助于阐明为什么皮质类固醇试验以前失败以及为什么TBI后孕酮治疗可能是有益的。
Despite significant advances in the management of head trauma, there remains a lack of pharmacological treatment options for traumatic brain injury (TBI). While progesterone clinical trials have shown promise, corticosteroid trials have failed. The purpose of this study was to (1) characterize endogenous cerebrospinal fluid (CSF) progesterone and cortisol levels after TBI, (2) determine relationships between CSF and serum profiles, and (3) assess the utility of these hormones as predictors of long-term outcomes. We evaluated 130 adults with severe TBI. Serum samples (n=538) and CSF samples (n=746) were collected for 6 days post-injury, analyzed for cortisol and progesterone, and compared with healthy controls (n=13). Hormone data were linked with clinical data, including Glasgow Outcome Scale (GOS) scores at 6 and 12 months. Group based trajectory (TRAJ) analysis was used to develop temporal hormone profiles delineating distinct subpopulations. Compared with controls, CSF cortisol levels were significantly and persistently elevated during the first week after TBI, and high CSF cortisol levels were associated with poor outcome. As a precursor to cortisol, progesterone mediated these effects. Serum and CSF levels for both cortisol and progesterone were strongly correlated after TBI relative to controls, possibly because of blood-brain barrier disruption. Also, differentially impaired hormone transport and metabolism mechanisms after TBI, potential de novo synthesis of steroids within the brain, and the complex interplay of cortisol and pro-inflammatory cytokines may explain these acute hormone profiles and, when taken together, may help shed light on why corticosteroid trials have previously failed and why progesterone treatment after TBI may be beneficial.